DESCRIPTION: This is a new proposal, the intention is to investigate At, regulated apoptosis with the ultimate goal of elucidating downstream effectors of Atm signaling. The proposal is based on preliminary data indicating that specific populations of dividing cells in the Atm knockout nervous system are protected from the pro-apoptotic effects of ionizing radiation. The aims of the application will be to identify potential physiologically relevant activators (oxidative stress, excitotoxicity, axotomy) of the Atm signaling pathway by using Atm -/- mice and neuronal cell cultures derived from these animals; to identify components of the apoptotic pathway involving Atm and the nervous system by using the Atm -/- mice as well as p53, Bcl-2 and Bax -/- mice, and cultures derived from these animals and finally, to exhaustively investigate and characterize the developing nervous system in the Atm -/- mice and to ask whether Atm is important for normal programmed cell death.